Premium
Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide
Author(s) -
Park JiYoung,
Kim KyoungAh,
Park PilWhan,
Park ChanWoong,
Shin JaeGook
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00221-2
Subject(s) - gliclazide , pharmacokinetics , pharmacodynamics , pharmacology , medicine , rifampicin , crossover study , placebo , diabetes mellitus , endocrinology , tuberculosis , alternative medicine , pathology
Objective Our objective was to investigate the effect of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of gliclazide, a sulfonylurea antidiabetic drug. Method In a randomized 2‐way crossover study with a 4‐week washout period, 9 healthy Korean subjects were treated once daily for 6 days with 600 mg rifampin or with placebo. On day 7, a single dose of 80 mg gliclazide was administered orally. Plasma gliclazide, blood glucose, and insulin concentrations were measured. Results Rifampin decreased the mean area under the plasma concentration–time curve for gliclazide by 70% ( P < .001) and the mean elimination half‐life from 9.5 to 3.3 hours ( P < .05). The apparent oral clearance of gliclazide increased about 4‐fold after rifampin treatment ( P < .001). A significant difference in the blood glucose response to gliclazide was observed between the placebo and rifampin phases. Conclusion The effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide suggests that rifampin affects the disposition of gliclazide in humans, possibly by the induction of cytochrome P450 2C9. Concomitant use of rifampin with gliclazide can considerably reduce the glucose‐lowering effects of gliclazide. Clinical Pharmacology & Therapeutics (2003) 74 , 334–340; doi: 10.1016/S0009‐9236(03)00221‐2